The 2-[(2-pyridyl)methylsulfinyl]benzimidazole compounds such as omeprazole or lansoprazole are potent antiulcer agents, and are used as pharmaceutical compositions for oral administration. Further, the injections thereof have recently been developed.
As an injection of omeprazole, there has been known an injection prepared by dissolving sodium salt of omeprazole in sterilized water, filtering and lyophilizing the solution to give a lyophilized product, and then dissolving the lyophilized product in a mixture of polyethylene glycol 400 for injection, sodium dihydrogenphosphate and sterilized water (Japanese Patent Unexamined Publication No. 167587/1984).
Also, an injection prepared by dissolving a lyophilized product of an alkaline aqueous solution of a 2-[(2-pyridyl)methylsulfinyl]benzimidazole compound having antiulcer activity such as lansoprazole in a mixture of (a) acid, and (b) at least one of ethanol, propylene glycol and polyethylene glycol (Japanese Patent Unexamined Publication No. 138213/1990).
In general, the pH of injection is preferably about 4-8, and a pH above 9 has a probability of causing hemolysis and local irritation.
In the case of the 2-[(2-pyridyl)methylsulfinyl]benzimidazole compound or a salt which may be hereinafter referred to as "benzimidazole compound or salt thereof" represented by sodium salt of omepazole, it shows a solubility of the level permitting formulation of the preparation, in water in an alkaline range of pH 9.5 or above, whereas it shows extremely low solubility in water at a pH of not more than 9, thus rendering formulation of the preparation very difficult.
While the benzimidazole compound or salt thereof is stable in the alkaline range, it poses a problem in that its stability decreases with the low ph values.
For this reason, the method employed in conventional injections of benzimidazole compound or salt thereof such as sodium salt of omeprazole has been to add an acid such as hydrochloric acid or sodium dihydrogenphosphate to the solution to keep the pH from neutral to weak basic, and to further add a nonaqueous solvent such as polyethylene glycol, ethanol or propylene glycol in order to obtain a certain level of solubility in such pH range.
Yet, these injections pose problems of local irritation and hemolysis caused by the nonaqueous solvent added to the solution for dissolution.
Accordingly, an object of the invention is to provide an injection of a benzimidazole compound or a salt thereof, particularly sodium salt of omeprazole causing less side-effects such as hemolysis, and less local irritation, which salt permits easy formulation.